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Free Extracellular miRNA Functionally Targets Cells by Transfecting Exosomes from Their Companion Cells.
- Source :
-
PloS one [PLoS One] 2015 Apr 29; Vol. 10 (4), pp. e0122991. Date of Electronic Publication: 2015 Apr 29 (Print Publication: 2015). - Publication Year :
- 2015
-
Abstract
- Lymph node and spleen cells of mice doubly immunized by epicutaneous and intravenous hapten application produce a suppressive component that inhibits the action of the effector T cells that mediate contact sensitivity reactions. We recently re-investigated this phenomenon in an immunological system. CD8+ T lymphocyte-derived exosomes transferred suppressive miR-150 to the effector T cells antigen-specifically due to exosome surface coat of antibody light chains made by B1a lymphocytes. Extracellular RNA (exRNA) is protected from plasma RNases by carriage in exosomes or by chaperones. Exosome transfer of functional RNA to target cells is well described, whereas the mechanism of transfer of exRNA free of exosomes remains unclear. In the current study we describe extracellular miR-150, extracted from exosomes, yet still able to mediate antigen-specific suppression. We have determined that this was due to miR-150 association with antibody-coated exosomes produced by B1a cell companions of the effector T cells, which resulted in antigen-specific suppression of their function. Thus functional cell targeting by free exRNA can proceed by transfecting companion cell exosomes that then transfer RNA cargo to the acceptor cells. This contrasts with the classical view on release of RNA-containing exosomes from the multivesicular bodies for subsequent intercellular targeting. This new alternate pathway for transfer of exRNA between cells has distinct biological and immunological significance, and since most human blood exRNA is not in exosomes may be relevant to evaluation and treatment of diseases.
- Subjects :
- Animals
Antibodies immunology
CD8-Positive T-Lymphocytes metabolism
Cell Line
Exosomes immunology
Humans
Lymphocyte Activation
Mice, Inbred C57BL
MicroRNAs isolation & purification
Toll-Like Receptor 3 immunology
Transfection
CD8-Positive T-Lymphocytes immunology
Exosomes genetics
MicroRNAs genetics
MicroRNAs immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 10
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 25923429
- Full Text :
- https://doi.org/10.1371/journal.pone.0122991